The guanine-nucleotide binding regulatory proteins (G-proteins) are a1b1g1 heterotrimers which function as transmembrane signal transducers by coupling receptors for extracellular stimuli to intracellular effectors (enzymes, ion channels). G-proteins constitute a diverse family distinguished by specific receptor and effector interactions which in turn are determined by the structure of the three constituent subunits. The a subunit binds guanine nucleotides and has a well established role in effector modulation. The b and g subunits are tightly associated as a bg complex, comprising a single functional entity which, like the a subunit, is absolutely required for G-protein interaction with receptor. An effector modulatory role for the bg complex is becoming increasingly apparent in several systems. The present research emphasizes the role of the bg complex in G-protein-mediated signal transduction. During this year the effector functional properties of the Gb5 isoform as well as a series of Gb1 coiled-coil point mutants were studied in transiently transfected COS cells. It was learned that the structurally distinct Gb5 isoform, while competent to regulate PLC-b signalling, was not able to activate the ERK2/MAPK or JNK signalling cascades as Gb1 could. In addition we found that a D20K point mutation in Gb1 facilitated JNK but not PLC-b signalling. Taken together these findings suggest that the mechanism by which Gbg modulates various effector targets differs among the effectors. The findings also implicate the Gbg coiled-coil in the mechanism of JNK activation. These studies may help elucidate the mechanism(s) by which the bg subunit complex modulates structurally diverse effector molecules pursuant to agonist stimulation.